Abstract Gut-associated lymphoid tissue (GALT) is known as a site for generation of the primary antibody repertoire in species such as rabbits and chickens. This repertoire develops early in life through an innate-like process in which B cells are stimulated in a non-antigen-specific manner. We will test the hypothesis that a similar GALT-like B cell developmental pathway is conserved in humans, and can be found in the appendix early in life. In collaboration with Drs. Donna Farber at Columbia U. and Eline Luning Prak at U. Penn, we will identify CD27+ B cell subsets in appendix from children, localize these subsets by immunofluorescence analysis, and perform Next Generation Sequencing to determine the ontogeny of the subsets. The nucleotide sequences will be compared with those from spleen to determine if the appendix B cells have increased somatic diversification in BCR, altered VH gene usage, and evidence of altered positive or negative selection. Results from this study are expected to provide evidence for a novel innate-like mechanism that contributes to generation of the antibody repertoire in humans.